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High-Dose ERT, Rituximab, and Early HSCT in an Infant with Wolman's Disease
Siawosh K Eskandari1, Elisabeth G M Revenich1, Dirk J Pot1
1From the Department of Metabolic Diseases, Beatrix Children's Hospital (S.K.E., F.B., F.J.S., C.M.A.L.), and the Department of Surgery (S.K.E.), University Medical Center (UMC) Groningen, Groningen, the Division of Pediatrics (E.G.M.R., M.B., P.M.H., C.A.L.) and the Department of Metabolic Diseases (P.M.H.), UMC Utrecht, and the Department of Stem Cell Transplantation, Princess Máxima Center for Pediatric Oncology (E.G.M.R., M.B., C.A.L.), Utrecht, and the Department of Pediatrics, Gelre Hospital, Apeldoorn (D.J.P.) - all in the Netherlands.
Insights
This study details a successful treatment for Wolman's disease, a fatal infant condition. An infant received enzyme-replacement therapy and B-cell depletion as a bridge to hematopoietic stem-cell transplantation, achieving a disease-free state.
Area of Science:
- Biochemistry
- Genetics
- Immunology
Background:
- Wolman's disease is a fatal lysosomal acid lipase deficiency causing lipid accumulation.
- Current treatments like enzyme-replacement therapy (ERT) have limitations and may wane over time.
- Hematopoietic stem-cell transplantation (HSCT) offers a definitive solution but carries significant risks.
Purpose of the Study:
- To describe a novel therapeutic strategy for an infant with Wolman's disease.
- To evaluate the efficacy of ERT, dietary fat restriction, and rituximab as a bridge to HSCT.
- To assess long-term outcomes and donor chimerism post-HSCT.
Main Methods:
- High-dose enzyme-replacement therapy (ERT) combined with dietary fat restriction.
- Rituximab-based B-cell depletion therapy.
- Allogeneic hematopoietic stem-cell transplantation (HSCT) performed early in infancy.
Main Results:
- The infant was successfully bridged to HSCT using the combined therapeutic approach.
- At 32 months, the patient was independent of ERT and showed no signs of disease.
- Complete donor chimerism (100%) was achieved in the peripheral blood post-HSCT.
Conclusions:
- This combined strategy of ERT, B-cell depletion, and early HSCT can be a viable and effective treatment for Wolman's disease.
- Achieving disease-free status and donor chimerism suggests long-term therapeutic success.
- This approach may offer a safer and more definitive alternative to traditional HSCT protocols for this rare condition.
Abstract:
Wolman's disease, a severe form of lysosomal acid lipase deficiency, leads to pathologic lipid accumulation in the liver and gut that, without treatment, is fatal in infancy. Although continued enzyme-replacement therapy (ERT) in combination with dietary fat restriction prolongs life, its therapeutic effect may wane over time. Allogeneic hematopoietic stem-cell transplantation (HSCT) offers a more definitive solution but carries a high risk of death. Here we describe an infant with Wolman's disease who received high-dose ERT, together with dietary fat restriction and rituximab-based B-cell depletion, as a bridge to early HSCT. At 32 months, the infant was independent of ERT and disease-free, with 100% donor chimerism in the peripheral blood.
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